Division of Hematology/Oncology, Northwestern University, 676 North St. Clair Street, Suite 850, Chicago, IL 60611, USA.
Breast Cancer Res Treat. 2012 Apr;132(3):833-42. doi: 10.1007/s10549-011-1411-8. Epub 2011 Feb 27.
Lapatinib, a dual kinase inhibitor against epidermal growth factor receptor (EGFR) and human epidermal receptor two (HER2) has shown efficacy in treating HER2 positive breast cancer. Nanoparticle albumin bound (nab) paclitaxel was developed to reduce toxicities from paclitaxel and improve its efficacy. Thirty patients with stage I-III HER2 positive breast cancer were treated in the neoadjuvant setting with lapatinib 1,000 mg/day and nab-paclitaxel 260 mg/m(2) every 3 weeks for four cycles. The primary end point of the trial was clinical response rate (cRR) with secondary end points including pathologic complete response rate (pCR), tolerability of the combination, and marker response. The cRR was 82.8% (24 patients) with six (20.7%) patients having complete clinical response, 18 (62.1%) having partial clinical response, and five (17.2%) stable disease. A pCR was observed in five of the 28 patients (17.9%). The most frequent grade 2 toxicities were neuropathy in nine patients (30%), fatigue in seven patients (23.3%), rash in 11 patients (36.7%), and bone pain in 10 patients (33.3%). There was no significant drop in the left ventricular ejection fraction (LVEF). Of the tissue markers examined, we were not able to find a predictor of response. The combination of lapatinib and nab-paclitaxel was well tolerated and provided good efficacy in women with HER2 positive breast cancer. This combination offers an alternative non-anthracycline-containing regimen for women with HER2 positive breast cancer.
拉帕替尼是一种针对表皮生长因子受体（EGFR）和人表皮受体 2（HER2）的双重激酶抑制剂，已被证明在治疗 HER2 阳性乳腺癌方面有效。纳米白蛋白结合型紫杉醇（nab-紫杉醇）的开发旨在降低紫杉醇的毒性并提高其疗效。30 例 I-III 期 HER2 阳性乳腺癌患者接受新辅助治疗，每日给予拉帕替尼 1000mg 和 nab-紫杉醇 260mg/m2，每 3 周一次，共 4 个周期。试验的主要终点是临床缓解率（cRR），次要终点包括病理完全缓解率（pCR）、联合治疗的耐受性和标志物反应。cRR 为 82.8%（24 例），其中 6 例（20.7%）患者完全临床缓解，18 例（62.1%）患者部分临床缓解，5 例（17.2%）患者疾病稳定。28 例患者中有 5 例（17.9%）观察到 pCR。最常见的 2 级毒性是 9 例患者（30%）的神经病变、7 例患者（23.3%）的疲劳、11 例患者（36.7%）的皮疹和 10 例患者（33.3%）的骨痛。左心室射血分数（LVEF）无明显下降。在检查的组织标志物中，我们未能找到反应的预测因子。拉帕替尼和 nab-紫杉醇的联合应用耐受性良好，对 HER2 阳性乳腺癌患者疗效良好。该联合方案为 HER2 阳性乳腺癌患者提供了一种替代的不含蒽环类药物的治疗方案。
